Von Willebrand Factor (VWF)-targeting agents and methods of using the same

Abstract

Provided herein are aptamers capable of inhibiting the activity of Von Willebrand Factor (VWF). Pharmaceutical compositions comprising these aptamers are also provided. Methods of preventing blood clot formation in a subject by administering the aptamers are provided and methods of treating a blood clot by administering a VWF-targeting agent are also provided.

We claim: 
     
       1. An antidote comprising a polynucleotide having at least 90% sequence identity to SEQ ID NO: 157, wherein the antidote is no more than 24 nucleotides in length. 
     
     
       2. An antidote comprising a polynucleotide having sequence reverse complementary to and capable of hybridizing to at least 8 nucleotides of an aptamer comprising a polynucleotide of SEQ ID NO: 3, or a polynucleotide with at least 90% sequence identity to SEQ ID NO: 3 and wherein the antidote is no more than 24 nucleotides in length. 
     
     
       3. A pharmaceutical composition comprising a pharmaceutical carrier and any one of the antidotes of  claim 1 . 
     
     
       4. A method for preventing blood clot formation in a subject comprising administering to the subject a composition comprising a polynucleotide of SEQ ID NOs: 3, or a polynucleotide with at least 90% sequence identity to SEQ ID NO: 3, in a therapeutically effective amount to prevent blood clot formation in the subject and further administering to the subject an antidote of  claim 1  in a therapeutically effective amount to neutralize the composition. 
     
     
       5. The method of  claim 4 , wherein the subject suffers from atrial fibrillation or is at risk of having a Deep Vein Thrombosis, a stroke, a heart attack, or a pulmonary embolism. 
     
     
       6. The method of  claim 4 , wherein the subject is a mammal. 
     
     
       7. The method of  claim 6 , wherein the mammal is a human. 
     
     
       8. A pharmaceutical composition comprising a pharmaceutical carrier and any one of the antidotes of  claim 2 . 
     
     
       9. A method for preventing blood clot formation in a subject comprising administering to the subject a composition comprising a polynucleotide of SEQ ID NOs: 3, or a polynucleotide with at least 90% sequence identity to SEQ ID NO: 3 in a therapeutically effective amount to prevent blood clot formation in the subject and further administering to the subject an antidote of  claim 2  in a therapeutically effective amount to neutralize the composition. 
     
     
       10. The method of  claim 9 , wherein the subject suffers from atrial fibrillation or is at risk of having a Deep Vein Thrombosis, a stroke, a heart attack, or a pulmonary embolism. 
     
     
       11. The method of  claim 9 , wherein the subject is a mammal. 
     
     
       12. The method of  claim 11 , wherein the mammal is a human. 
     
     
       13. A method of neutralizing an aptamer in a subject, the method comprising administering an antidote of  claim 1  to a subject who has received a composition comprising an aptamer comprising a polynucleotide of SEQ ID NOs: 3, or a polynucleotide with at least 90% sequence identity to SEQ ID NO: 3 wherein the antidote is administered in a therapeutically effective amount to neutralize the composition. 
     
     
       14. The method of  claim 13 , wherein the subject suffers from atrial fibrillation or is at risk of having a Deep Vein Thrombosis, a stroke, a heart attack, or a pulmonary embolism. 
     
     
       15. A method of neutralizing an aptamer in a subject, the method comprising administering an antidote of  claim 2  to a subject who has received a composition comprising an aptamer comprising a polynucleotide of SEQ ID NOs: 3, or a polynucleotide with at least 90% sequence identity to SEQ ID NO: 3 wherein the antidote is administered in a therapeutically effective amount to neutralize the composition. 
     
     
       16. The method of  claim 15 , wherein the subject suffers from atrial fibrillation or is at risk of having a Deep Vein Thrombosis, a stroke, a heart attack, or a pulmonary embolism. 
     
     
       17. The method of  claim 15 , wherein the subject is a mammal. 
     
     
       18. The method of  claim 17 , wherein the mammal is a human. 
     
     
       19. An antidote comprising a polynucleotide capable of hybridizing to 8 to 24 nucleotides of an aptamer of SEQ ID NO: 3 and having at least 80% sequence identity to SEQ ID NO: 157 and wherein the antidote is no more than 24 nucleotides in length. 
     
     
       20. A method of neutralizing an aptamer in a subject, the method comprising administering the antidote of  claim 19  to a subject who has received a composition comprising an aptamer, wherein the aptamer is a polynucleotide of SEQ ID NO:3, or a polynucleotide with at least 90% sequence identity to SEQ ID NO: 3, and wherein the antidote is administered in a therapeutically effective amount to neutralize the composition.